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πŸ“ Lactate, Not Pyruvate, Is The End Product Of Glucose Metabolism Via Glycolysis

Glucose is the monosaccharide utilized by most eukaryotes to generate metabolic energy, and in the majority of eukaryotic systems, glycolysis is the first biochemical pathway where glucose breaks down via a series of enzymatic reactions to produce relatively small amounts of adenosinetriphosphate (ATP). In 1940, the sequence of these glycolytic reactions was elucidated, a breakthrough that was recognized as the very first such elucidation of a biochemical pathway in history. Accordingly, the glycolytic breakdown of glucose ends up either with pyruvate as the final product under aerobic conditions or with lactate, to which pyruvate is being reduced, under anaerobic conditions. Consequently, pyruvate has been designated and is held to be the substrate of the mitochondrial tricarboxylic acid cycle, where it is completely oxidized into CO2 and H2O, while lactate has been defined and being held to as a useless dead-end product, poisonous at times, of which cells must discard off quickly. More than four decades after the glycolytic pathway has been elucidated, studies of both muscle and brain tissues have suggested that lactate is not necessarily a useless end product of anaerobic glycolysis and may actually play a role in bioenergetics. These studies have shown that muscle and brain tissues can oxidize and utilize lactate as a mitochondrial energy substrate. These results have been met with great skepticism, but a large number of publications over the past quarter of a century have strengthened the idea that lactate does play an important and, possibly, a crucial role in energy metabolism. These findings have shed light on a major drawback of the originally proposed aerobic version of the glycolytic pathway, that is, its inability to regenerate nicotinamide adenine dinucleotide (oxidized form) (NAD+ ), as opposed to anaerobic glycolysis that features the cyclical ability of the glycolytic lactate dehydrogenase (LDH) system to regenerate NAD+ upon pyruvate reduction to lactate. An examination of scientific investigations on carbohydrate metabolism of brain tissue in the 1920s and 1930s has already revealed that lactate can be readily oxidized. However, due to the prevailing dogma, according to which lactate is a waste product, its oxidation was assumed to be a possible mechanism of elimination. This chapter examines both old and new research data on glucose glycolysis both in muscle and in brain tissues. This chapter consolidates the available data in an attempt to form a more accurate and clear description of this universal and very important bioenergetic chain of reactions.

Updated on June 7, 2020

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